title: The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF-α.
abstract: The P2×7 receptor (P2×7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL-1β release. Since innate immune activation and IL-1β release seem to be implicated in Behçet's disease (BD), a systemic immune-inflammatory disorder of unknown origin, we hypothesized that P2×7r is involved in the pathogenesis of the disease. Monocytes were isolated from 18 BD patients and 17 healthy matched controls. In BD monocytes, an increased P2×7r expression and Ca(2+) permeability induced by the selective P2×7r agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL-1β release from LPS-primed monocytes stimulated with BzATP was markedly higher in BD patients than in controls. TNF-α-incubated monocytes from healthy subjects almost reproduced the findings observed in BD patients, as demonstrated by the increase in P2×7r expression and BzATP-induced Ca(2+) intake. Our results provide evidence that in BD monocytes both the expression and function of the P2×7r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF-α on the receptor. These data indicate P2×7r as a new potential therapeutic target for the control of BD, further supporting the rationale for the use of anti-TNF-α drugs in the treatment of the disease.
authors.affiliation: Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Castrichini
authors.forename: Pietro Enea
authors.initials: PE
authors.lastname: Lazzerini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gamberucci
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.forename: Rossella
authors.initials: R
authors.lastname: Franceschini
authors.forename: Mariarita
authors.initials: M
authors.lastname: Natale
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hammoud
authors.forename: Antonio
authors.initials: A
authors.lastname: Moramarco
authors.forename: Stefania
authors.initials: S
authors.lastname: Zimbone
authors.forename: Elena
authors.initials: E
authors.lastname: Gianchecchi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Montilli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ricci
authors.forename: Enrico
authors.initials: E
authors.lastname: Selvi
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi-Pasini
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D001528:Behcet Syndrome / Q000276:immunology*; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000378:metabolism*; D017136:Ion Transport; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D058486:Receptors, Purinergic P2X7 / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D058911:Purinergic P2X Receptor Agonists; D058486:Receptors, Purinergic P2X7; D014409:Tumor Necrosis Factor-alpha; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: Behçet's disease; IL-1β; Monocytes; P2 × 7 receptor; TNF-α